A New Measure Assessing Recovery from a Sickle Cell Crisis

Rationale: Vaso-occlusive crisis (VOC) is a recurring complication of sickle cell disease (SCD) and a common reason for emergency department visits and hospitalizations among SCD patients. Few qualitative studies on the symptoms and impacts of SCD have been published. Specifically, while the duration of hospitalization for VOC is well-documented, little is known about the patient experience of recovery from a VOC. The purpose of this research was to understand the experience of recovery from VOC from the patient's perspective and to develop a brief measure to assess recovery to be administered across age groups in future clinical trial programs.

Methods: A concept elicitation (CE) study consisted of face-to-face, one-on-one interviews with SCD patients, and caregivers of patients hospitalized for a VOC within 90 days prior to their interview. The semi-structured interview guide focused on the symptoms and impacts of VOC and the activities important to recovery following a VOC. A thematic analysis in MAXQDA qualitative software was conducted to identify key concepts. Results informed the development of a draft measure which was refined in two cognitive debriefing (CD) studies, one using interviewer administration format, and one using an electronic self-administration format. Interviews focused on the meaning and interpretation of the questionnaire instructions, items and responses, and feasibility of administration.

Results: The CE sample included 16 participants; 5 adults and adolescents, 6 children ages 8-11, and 5 caregivers of younger children. Patients/caregivers reported that pain is not completely eliminated at time of actual discharge but gradually resolves over the week following hospitalization. In addition to pain, fatigue and the effects of pain medication also affect functional status in the immediate post-hospitalization period. The types of activities impaired during recovery were physical activities, social activities, daily activities such as work or school, and self-care activities. This conceptual framework resulted in a draft "Return to Normal Activity Questionnaire" (RNAQ), with equivalent versions for each age group, including caregiver report. Although the precise item wording and activity examples differed slightly by age group, all three versions shared the same four domains and the same response scale; an 11-point NRS with anchors 0 = "Cannot do at all" to 10 = "Can do completely as usual." The first CD study included 9 patients (3 per age group) with the interviewer administering the RNAQ verbally. Based on these interviews, self-report was determined infeasible for children 8-11. Thus, caregiver report was recommended for all children under 12. The self-administered version of the RNAQ was debriefed in a sample of adult and adolescent patients (N=17). Based on participant feedback, the NRS scale was reversed so that 0 indicates best functioning, to be consistent with a familiar pain rating question frequently used in clinical practice to evaluate VOC severity. Most patients reported that the typical time to complete recovery ranged from 2 days to one week; thus daily administration for 7 days following VOC hospitalization was recommended.

Conclusions: The RNAQ was developed according to FDA PRO Guidance and appears to be appropriate for assessing recovery in SCD patients following a VOC hospitalization. Due to the small sample size in the first CD study, additional debriefing on the caregiver-reported version is recommended. In addition, psychometric validation is required to obtain full evidence of validity and to understand how to interpret RNAQ scores.